Chemotherapy-induced pica and anorexia are reduced by common hepatic branch vagotomy in the rat

Jonghe, Bart C. De; Horn, Charles C.

doi:10.1152/ajpregu.00820.2007

Cited by 52 publications

(62 citation statements)

References 62 publications

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“…Emesis induced by cisplatin is prevented by abdominal vagotomy in dogs (12), monkeys (13), and ferrets (17). In rats, cisplatin-induced pica is suppressed by 61% by common hepatic branch vagotomy (29). In contrast, bilateral subdiaphragmatic vagotomy in rats does not prevent subsequent acquisition of a conditioned taste aversion induced by LiCl (30).…”

Section: Discussionmentioning

confidence: 99%

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

et al. 2010

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Abstract. We investigated the effects of various emetic agents: cisplatin, apomorphine, lithium chloride (LiCl), rolipram, sibutramine, and the β 3 -adrenoceptor (AR) agonist CL316243 on salivary amylase secretion in rats. We also determined the inhibitory effect of granisetron, a 5-HT 3 -receptor antagonist, on cisplatin-induced increased salivary amylase activity and the inhibitory effect of bilateral abdominal vagotomy on increases in salivary amylase activity induced by cisplatin and LiCl. Granisetron was administered 15 min before and 1 h after cisplatin administration. Cisplatin (10 -15 mg/kg, i.v.) increased salivary amylase activity dose-dependently and induced an acute increase from 1.5 h post-treatment with 15 mg/kg. Apomorphine (1 -3 mg/kg, s.c.), LiCl (120 mg/kg, i.p.), rolipram (3 -10 mg/kg, p.o.), and sibutramine (10 mg/kg, p.o.) induced significant increases in salivary amylase secretion. On the other hand, CL316243 did not stimulate salivary amylase secretion. The increased amylase activity induced by cisplatin (15 mg/kg, i.v.) was inhibited significantly by granisetron (1 or 3 mg/kg × 2, i.v.) or tended to be inhibited by bilateral abdominal vagotomy, whereas an increase in amylase activity produced by LiCl was not inhibited by abdominal visceral nerve section. These results suggest that salivary amylase activity is useful as a marker for emesis in rats, a species that does not exhibit vomiting.

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Section: Discussionmentioning

confidence: 99%

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

et al. 2010

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“…To determine whether nausea/malaise contributes to the food intake-suppressive effects produced by VTA amylin receptor signaling, we availed of an established model of nausea/malaise (Alhadeff et al, 2012;Andrews and Horn, 2006;De Jonghe and Horn, 2008;Kanoski et al, 2012;Mitchell et al, 1976) by examining pica, the consumption of a non-nutritive substance (eg, kaolin silicate clay). Rats received counterbalanced intra-VTA injections of sCT (0, 0.004, 0.04, or 0.4 mg/100 nl aCSF) and intake of chow and kaolin were measured for 24 h. As in our previous experiment, the two highest doses of sCT tested (0.4 and 0.04 mg) reduced 24 h chow intake ( Figure 3a; ANOVA: F 3,18 ¼ 7.34, P ¼ 0.002; vehicle vs 0.04 or 0.4 mg, Po0.05) and 0.4 mg sCT reduced 24 h BW gain (Figure 3c; ANOVA: F 3,18 ¼ 3.38, P ¼ 0.04; vehicle vs 0.4 mg, Po0.05).…”

Section: Amylin Receptor Activation In the Vta Reduces Chow Intake Bymentioning

confidence: 99%

Amylin Receptor Signaling in the Ventral Tegmental Area is Physiologically Relevant for the Control of Food Intake

Mietlicki‐Baase

Rupprecht

Olivos

et al. 2013

Neuropsychopharmacol

116

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The ability of amylin, a pancreatic b-cell-derived neuropeptide, to promote negative energy balance has been ascribed to neural activation at the area postrema. However, despite amylin binding throughout the brain, the possible role of amylin signaling at other nuclei in the control of food intake has been largely neglected. We show that mRNA for all components of the amylin receptor complex is expressed in the ventral tegmental area (VTA), a mesolimbic structure mediating food intake and reward. Direct activation of VTA amylin receptors reduces the intake of chow and palatable sucrose solution in rats. This effect is mediated by reductions in meal size and is not due to nausea/malaise or prolonged suppression of locomotor activity. VTA amylin receptor activation also reduces sucrose selfadministration on a progressive ratio schedule. Finally, antagonist studies provide novel evidence that VTA amylin receptor blockade increases food intake and attenuates the intake-suppressive effects of a peripherally administered amylin analog, suggesting that amylin receptor signaling in the VTA is physiologically relevant for food intake control and potentially clinically relevant for the treatment of obesity.

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“…After three more days, they received an injection of cisplatin (6 mg ⅐ kg Ϫ1 ⅐ 2 ml Ϫ1 ). The timing and order of treatments was based on our previous studies showing no effects of the control injections on kaolin intake, no lasting effect of apomorphine treatment, and a significant longterm effect of cisplatin injection on food intake and body weight (10,12). Three days after the cisplatin injection, the animals were anesthetized (pentobarbital sodium, 50 mg ip, total per animal) and then euthanized by exsanguination and perfused using the method described for experiment 1. Histology.…”

Section: Experiments 2: Cisplatin-induced Pica In Lateral Pbn-lesionedmentioning

confidence: 99%

“…Similar to the action of cisplatin on emesis (1,7,50), cisplatin-induced kaolin consumption in the rat is largely dependent on an intact subdiaphragmatic vagus (10) and is inhibited by common antiemetic drugs, such as 5-HT 3 and NK 1 receptor antagonists, as well as by corticosteroids (29,49,60). Cisplatin also activates GI vagal afferent fibers in the rat and ferret, a response that is blocked by antagonism of 5-HT 3 receptors (15,24).…”

mentioning

confidence: 93%

“…We assessed the impact of lPBN lesions on cisplatin-induced kaolin intake, anorexia, water consumption, and body weight. We also compared the behavior of lPBN-lesioned animals with controls after apomorphine injections because this emetic drug and cisplatin apparently stimulate kaolin intake by different routes, blood-born and vagal afferent activation, respectively, as suggested by our previous work (10). On the basis of the position of the lPBN to connect hindbrain and forebrain viscerosensory pathways, we hypothesized that bilateral lesion of the lPBN would reduce both cisplatin-and apomorphine-induced kaolin intake.…”

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confidence: 99%

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Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat

Horn

Jonghe

Mátyás

et al. 2009

American Journal of Physiology-Regulatory, Integrative and Comp

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Horn CC, De Jonghe BC, Matyas K, Norgren R. Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat. Am J Physiol Regul Integr Comp Physiol 297: R1375-R1382, 2009. First published August 26, 2009 doi:10.1152/ajpregu.00284.2009.-Anticancer agents, such as cisplatin, stimulate nausea, vomiting, and behaviors indicative of malaise. Rats and mice do not possess a vomiting response, and, therefore, in these species, the ingestion of kaolin clay (a pica response) has been used as an index of malaise. In the rat, cisplatininduced kaolin intake is inhibited by antiemetic treatments. In addition, cisplatin activates vagal afferent fibers in the gut, and kaolin intake induced by cisplatin is largely dependent on an intact vagus. Nevertheless, little is known about the brain pathways controlling pica. We investigated the role of the lateral parabrachial nucleus (lPBN), a major visceral afferent link between the hindbrain and forebrain, in cisplatin-induced c-Fos expression and pica. Injection of cisplatin (6 mg/kg ip) produced c-Fos expression in the ventrolateral (external) lPBN, a region receiving viscerosensory input. In rats with bilateral ibotenic acid lPBN lesions, cisplatin treatment substantially increased kaolin intake compared with controls (ϳ30 g vs. ϳ5 g, respectively, over 24 h). Food intake was reduced by cisplatin treatment and by apomorphine, an emetic agent that acts centrally. Unlike cisplatin, however, apomorphine stimulated kaolin intake to a similar degree in both the lesioned and control rats, suggesting that lPBN damage neither produces nonspecific effects nor enhances malaise in general. These data suggest that lPBN-lesioned animals not only demonstrate pica after cisplatin treatment, but, in fact, show an exaggerated response that is greatly in excess of any treatment known to produce kaolin intake in rats.emesis; nausea; pica; vagus; anorexia CANCER CHEMOTHERAPY AGENTS, such as cisplatin, stimulate nausea, vomiting, anorexia, and other behaviors indicative of malaise (for a review, see Refs. 2, 21, 27, 51). Several species, including dogs, cats, ferrets, pigs, and shrews, have been used to study emesis after treatment with chemotherapy agents (16,18,31,33,58). In contrast, laboratory rats and mice appear to lack a vomiting response (see Ref. 2 for review). For these species, kaolin intake has been used as a proxy for emesis (60,64). A wide variety of stimuli, including cisplatin, induce kaolin consumption in rats (36,53,59,60,65). Like emesis, geophagia appears to be a defensive response. Clay may serve to bind or dilute a toxin in the gastrointestinal (GI) tract, thus reducing its adverse effects (45, 46). After injection with cisplatin, rats consuming kaolin show less body weight loss and a smaller reduction in food intake than rats without kaolin access (12). The consumption of clay by humans is also recognized as a potential detoxification strategy (48).Despite the use of kaolin intake as an index of malaise in rats, very little is known about...

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Chemotherapy-induced pica and anorexia are reduced by common hepatic branch vagotomy in the rat

Cited by 52 publications

References 62 publications

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

Various Emetogens Increase the Secretion of Salivary Amylase in Rats: a Potential Model in Emesis Research

Amylin Receptor Signaling in the Ventral Tegmental Area is Physiologically Relevant for the Control of Food Intake

Chemotherapy-induced kaolin intake is increased by lesion of the lateral parabrachial nucleus of the rat

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